NALOXONE HYDROCHLORIDE AND PENTAZOCINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause withdrawal in patients dependent on other opioids.
Pentazocine is a mixed agonist-antagonist opioid that binds to mu-opioid receptors (partial agonist) and kappa-opioid receptors (agonist), producing analgesia. Naloxone is a pure opioid antagonist that competitively blocks mu, kappa, and delta receptors; when administered orally, naloxone undergoes extensive first-pass metabolism, reducing systemic absorption and primarily blocking the effects of pentazocine if the combination is misused parenterally.
| Metabolism | Pentazocine is metabolized primarily by hepatic conjugation (glucuronidation) and oxidation via CYP2C19 and CYP2D6; naloxone is extensively metabolized by the liver, primarily via glucuronidation (UGT2B7). |
| Excretion | Pentazocine is primarily metabolized in the liver and excreted in urine as conjugates of glucuronide and sulfate, with about 60% of a dose excreted renally within 24 hours as metabolites and unchanged drug (less than 5% unchanged). Naloxone undergoes extensive hepatic metabolism to naloxone-3-glucuronide, which is excreted renally; approximately 50% of a dose is excreted as conjugates in urine within 6 hours. |
| Half-life | Pentazocine has an elimination half-life of 2-3 hours in healthy adults, which may be prolonged in patients with hepatic impairment. Naloxone has a terminal half-life of 0.5-1.5 hours in adults, with a rapid decline in plasma levels; the short half-life limits its duration of opioid antagonism. |
| Protein binding | Pentazocine: Approximately 35-65% bound to plasma proteins (mainly albumin). Naloxone: Approximately 32-45% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Pentazocine: Vd ~2-3 L/kg, indicating extensive tissue distribution. Naloxone: Vd ~2-3 L/kg, also indicating wide distribution. |
| Bioavailability | Oral pentazocine: 20-30% due to first-pass metabolism. Intramuscular pentazocine: 100%. Subcutaneous pentazocine: 100%. Oral naloxone: <2% due to extensive first-pass metabolism. Intramuscular and subcutaneous naloxone: 100%. Intravenous: 100% for both. |
| Onset of Action | Intravenous: Pentazocine has an onset of 2-3 minutes; naloxone 1-2 minutes. Intramuscular: Pentazocine 15-30 minutes; naloxone 2-5 minutes. Subcutaneous: Pentazocine 15-30 minutes; naloxone 5 minutes. Oral: Pentazocine 15-30 minutes; naloxone undergoes extensive first-pass metabolism, so oral bioavailability is low (<2%) and onset is not clinically relevant. |
| Duration of Action | Pentazocine: Analgesic effects last 3-4 hours after IM/SC doses; respiratory depression may persist longer. Naloxone: Duration of opioid antagonism is 0.5-1 hour after IV administration, but may be shorter than the half-life of the opioid; repeated doses or continuous infusion may be needed. |
| Molecular Weight | Naloxone HCl: 363.8 Da; Pentazocine HCl: 329.9 Da; combination: not applicable |
Oral: One tablet (naloxone 0.5 mg / pentazocine 50 mg) every 3-4 hours as needed for pain; maximum 12 tablets daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: Administer every 6 hours; GFR 10-29 mL/min: Administer every 8-12 hours; GFR <10 mL/min: Administer every 12 hours or consider alternative. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% or extend interval; Child-Pugh Class C: Avoid use. |
| Pediatric use | Not recommended for children under 12 years. For older children (≥12 years): Pentazocine 50 mg (with naloxone 0.5 mg) orally every 3-4 hours as needed; maximum 6 tablets daily. |
| Geriatric use | Initiate with half the usual adult dose (one-half tablet) and titrate carefully due to increased sensitivity and risk of respiratory depression. |
| 1st trimester | Avoid use during first trimester unless absolutely necessary; pentazocine may cross placenta and risk of teratogenicity in animal studies, but human data limited. |
| 2nd trimester | Use only if potential benefit justifies risk; pentazocine may cause fetal respiratory depression and dependence. |
| 3rd trimester | Avoid use near term; pentazocine can cause neonatal respiratory depression, withdrawal syndrome, and may prolong labor. |
Clinical note
CNS depressants may enhance sedative effects Can cause withdrawal in patients dependent on other opioids.
| FDA category | Animal |
| Placental transfer | Both pentazocine and naloxone cross the human placenta; pentazocine reaches fetal plasma concentrations approximately 1/3 to 1/2 of maternal levels. |
■ FDA Black Box Warning
Risk of respiratory depression, particularly in elderly, cachectic, or debilitated patients; risk of addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risk of life-threatening respiratory depression when used with benzodiazepines or other CNS depressants.
| Common Effects | Dizziness |
| Serious Effects |
Hypersensitivity to naloxone or pentazocineAcute or severe bronchial asthmaRespiratory depression when antagonist not availableOpioid dependence with acute withdrawal syndrome (pentazocine may precipitate withdrawal)
| Precautions | Respiratory depression; hypotension; increased intracranial pressure; seizure risk (pentazocine); opioid-induced hyperalgesia; adrenal insufficiency; severe hypotension; interaction with MAOIs; risk of dependence and withdrawal; gastrointestinal obstruction; impaired renal or hepatic function; head injury. |
Loading safety data…
| Breastfeeding |
| Pentazocine is excreted into breast milk in small amounts; naloxone is poorly absorbed orally. Risk of infant sedation and respiratory depression is low but possible. Monitor infant for drowsiness and feeding difficulties. |
| Lactation Rating | L3 (Moderately Safe, use with caution) |
| Teratogenic Risk | Pentazocine crosses the placenta; naloxone has limited placental transfer. No well-controlled human studies. First trimester: Risk cannot be excluded; avoid if possible. Second/Third trimester: Chronic use may cause fetal dependence; neonatal withdrawal syndrome reported. High doses near term may cause neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal respiratory rate, blood pressure, heart rate, and level of consciousness during labor. Assess neonatal Apgar scores, respiratory effort, and signs of opioid withdrawal (irritability, tremors, vomiting, poor feeding) for at least 48 hours after delivery. |
| Fertility Effects | No specific human data on fertility effects. Animal studies with pentazocine show no impairment of fertility. Naloxone may antagonize endogenous opioid effects on reproductive hormones, but clinical significance unknown. |
| Food/Dietary |
| No specific food interactions are reported for this combination. However, grapefruit juice may theoretically affect metabolism via CYP3A4 (pentazocine is metabolized by CYP3A4), but clinical significance is unknown. Advise patients to maintain a consistent diet. |
| Clinical Pearls | Naloxone in this fixed-dose combination is included to deter opioid abuse by reversing euphoria. The pentazocine component is a mixed agonist-antagonist opioid; naloxone has poor oral bioavailability but becomes active parenterally, precipitating withdrawal in opioid-dependent individuals. Use with caution in patients with impaired renal or hepatic function. Monitor for respiratory depression, especially in opioid-naive patients, as pentazocine alone can cause respiratory depression. |
| Patient Advice | Take exactly as prescribed; do not crush or inject tablets, as injected naloxone can cause severe withdrawal in opioid-dependent individuals. · This medication contains naloxone to discourage misuse; injection will cause withdrawal symptoms. · Report any signs of withdrawal (e.g., nausea, vomiting, sweating, agitation) or breathing difficulty. · Avoid alcohol and other central nervous system depressants as they increase risk of respiratory depression. · Do not use with other opioids unless directed, as effects are unpredictable. · Keep out of reach of children; accidental ingestion may cause severe respiratory depression. |